Project Summary/Abstract: The brain is able to perform complex processes through communication across functionally distinct brain regions. Neural oscillations, or brain waves/rhythms, including those in the gamma frequency range (~25 ? 140 Hz), may play a critical role in this form of communication. Neural oscillations represent periodic, synchronous activity across large groups of neurons. When oscillations in one region are synchronous with oscillations in another, their neuronal activity is temporally aligned, and thus region-to-region communication is facilitated. In this way, oscillatory synchrony may gate the flow of information between specific regions of the brain, creating transient ensembles unique to given brain processes. Importantly, this modulation of connectivity is rapid, reversible, and independent of physical changes to the underlying circuitry. Recent evidence suggests that the rodent hippocampus may utilize gamma oscillations in this way for proper memory function. Gamma oscillations in the hippocampus occur as two variants ? a slow gamma form (~25 ? 55 Hz) and a fast gamma form (~65 ? 140 Hz). Each variant occurs at separate times and synchronizes anatomically distinct hippocampal sub-regions. Specifically, slow gamma links areas CA3 and CA1, a circuit implicated in memory retrieval, while fast gamma links the medial entorhinal cortex (MEC) and CA1, a circuit thought necessary for memory encoding. We therefore hypothesize that slow gamma synchrony enhances CA1 ? CA3 communication and is necessary for proper memory retrieval, while fast gamma synchrony enhances MEC ? CA1 communication and is necessary for proper memory encoding. This hypothesis will be tested by examining differences in oscillatory and single cell activity in the hippocampus during each memory function (retrieval and encoding) in awake freely behaving rats. We expect to see enhanced fast gamma activity during memory encoding and enhanced slow gamma activity during memory retrieval. Specific Aim 1 will examine this hypothesis at the cellular level by measuring the activity of place cells, which represent the `where' component of memory. These cells exhibit unique firing properties during memory encoding vs. memory retrieval, providing a convenient method for determining the effects of slow and fast gamma on different memory functions. Specific Aim 2 will examine this hypothesis at the behavioral level by measuring fast and slow gamma activity in freely behaving rats performing a simple learning task, object recognition. In this task, increased exploration of novel objects compared to familiar objects indicates that memory formation of the familiar objects has occurred. Thus, explorations of novel and familiar objects serve as behavioral assays of memory encoding and retrieval, respectively. The results of the proposed experiments are expected to provide insights into the link between oscillatory activity and complex brain function, and lead to a deeper understanding of the role of aberrant oscillations in the generation of cognitive dysfunction.